Lipoprotein composition and metabolism in Pima Indians are being investigated to understand control of lipoprotein metabolism and how lipoproteins are related to obesity, insulin resistance and cardiovascular disease. Kinetic methods have been developed for the simultaneous study of VLDL, IDL, and LDL metabolism, for the short-term study of VLDL triglyceride metabolism, and for the in vitro evaluation of the binding properties of LDL. Studies of the relationships between lipoproteins and insulin-mediated glucose disposal indicated that there is a significant positive correlation between VLDL and insulin resistance, and a significant negative correlation between HDL concentrations and insulin resistance. These correlations were stronger in men than in women and were independent of each other. When the relationships between VLDL triglyceride and VLDL apoB metabolism were examined, the data suggested that in obese subjects hyperinsulinemia or insulin resistance induces overproduction of both VLDL apoB and triglyceride, whereas in diabetes VLDL triglyceride production is stimulated through increases in plasma free fatty acids or glucose. Obesity in the Pimas had a stronger influence on HDL in women, and the changes in HDL in obese women were associated with decreases in plasma estradiol and increases in hepatic lipase activities. Our studies on HDL suggest that HDL concentrations are related to both sex hormones and also to measures of insulin resistance and that men and women may differ with respect to the relative importance of these factors.